Pulmonary effects in man of oral prizidilol hydrochloride (SK&F 92657), a new antihypertensive agent.

The effects on heart rate, blood pressure and pulmonary function of single oral doses of prizidilol hydrochloride (400 mg SK&F 92657) and propranolol (40 mg) were compared with placebo in nine healthy volunteers, in a double blind crossover study. Prizidilol had no effect on heart rate while propranolol caused a significant reduction compared with placebo. Diastolic blood pressure was lowered to the same extent by both prizidilol and propranolol. Propranolol significantly reduced the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the maximal expiratory flow at 50% vital capacity (MEF 50). Prizidilol had no effect on flow-volume loop parameters. Effective pulmonary blood flow was not altered by propranolol, but it was significantly increased by prizidilol. Oral prizidilol exerts its hypotensive effect by vasodilatation without reflex tachycardia. It does not cause airways obstruction in healthy subjects.

Cardiovascular effects in man of intravenous prizidilol hydrochloride (SK&F 92657); a new antihypertensive agent.

1 Cardiovascular responses to intravenous prizidilol hydrochloride (SK&F 92657) 0.86 mg/kg were studied in eight supine resting healthy volunteers. Five subjects were slow and the remaining three were fast acetylators of sulphamethazine. Compared with pre-infusion values, mean resting systolic and diastolic blood pressures were significantly reduced, while mean resting pulse rate was significantly increased at 30 min after the start of the twenty minute infusion. 2 During the 6 h study period the lowest mean +/- s.e. mean systolic blood pressure (108.8 +/- 1.7) was recorded 30 min after the start of the infusion. This represented a mean reduction of 5.2 mmHg. Reductions in mean diastolic blood pressure were greater and of longer duration, the lowest mean value (44.8 +/- 2.0 mmHg) being recorded 3.5 h after the start of the infusion and representing a reduction of 18.5 mmHg from the pre-dosing value. At 6 h after the start of the infusion mean diastolic blood pressure was still significantly reduced (by 15.3 mmHg). 3 The maximum mean +/- s.e. mean resting pulse rate (79.3 +/- 4.4 beats/min) occurred 3 h after the start of the infusion, an increase of 23.0 beats/min over the pre-infusion value. At the end of the study the pulse rate was still significantly raised (by 17.7 beats/min). 4 The left ventricular ejection fraction, evaluated in five subjects, 45 min after the start of the infusion, was not altered by prizidilol hydrochloride, but the left ventricular area decreased significantly. 5 Intravenous prizidilol hydrochloride decreases resting blood pressure and left ventricular area, increases pulse rate and has virtually no effect on left ventricular ejection fraction.

Comparison of prizidilol hydrochloride (SK & F 92657), a new antihypertensive agent with beta-adrenoceptor antagonist and vasodilator activity with propranolol and hydralazine in normal volunteers.

1 Some cardiovascular pharmacology of prizidilol hydrochloride, a new antihypertensive compound with precapillary vasodilator and beta-adrenoceptor antagonist activity, in man is described. 2 To investigate further the pharmacological profile of this drug the effects of a single oral dose of 400 mg prizidilol hydrochloride were compared with propranolol 40 mg in combination with either 25 mg or 50 mg of hydralazine for up to 6 h after dosing, in a placebo controlled in eight healthy subjects. 3 Prizidolol hydrochloride significantly reduced supine and standing diastolic blood pressure and was more effective than propranolol combined with either dose of hydralazine in this respect. 4 Supine heart rate was significantly increased after prizidilol hydrochloride, but was not significantly changed after propranolol combined with either dose of hydralazine. The reasons for the increase in supine heart rate after prizidolol are discussed. 5 beta-adrenoceptor antagonism was assessed in terms of inhibition of exercise induced increases in heart rate and systolic blood pressure. At the doses used, prizidolol hydrochloride was less effective than propranolol and hydralazine combined, particularly during the first 3 h after dosing.

Urinary and serum octopamine in patients with portal-systemic encephalopathy.

Urinary excretion and serum concentrations of octopamine were studied in seventeen controls, thirty-three patients with portal-systemic encephalopathy, and thirteen patients with liver disease without encephalopathy. No differences were detected between control subjects and patients without encephalopathy. Urinary excretion and serum concentrations of octopamine were significantly higher in patients with encephalopathy compared with those without encephalopathy. The presence and grade of portal-systemic encephalopathy seemed to correlate more closely with the serum-octopamine concentrations than with urinary octopamine excretion. It is postulated that octopamine may be involved in the pathogenesis of portal-systemic encephalopathy.

Impaired cardiovascular responsiveness in liver disease.

Cardiovascular responsiveness to reflex impaired in patients with cirrhosis compared with control subjects. Peripheral vascular responses to exogenous noradrenaline were also impaired in cirrhotic patients, but peripheral vascular responses to infused adrenaline and to angiotensin II were similar in both groups. Impaired cardiovascular reactivity in patients with chronic liver disease could predispose them to circulatory failure after haemorrhage or surgery and should be considered when prescribing drugs which affect autonomic activity.